Acetaldehyde (systematic name ethanal) is an organic chemical compound with the formulaCH3CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and may be a contributing factor to hangovers from alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke.[10] Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

In the 1970s, the world capacity of the Wacker-Hoechst direct oxidation process exceeded 2 million tonnes annually.

Smaller quantities can be prepared by the partial oxidation of ethanol in an exothermic reaction. This process typically is conducted over a silver catalyst at about 500–650°C.[19]

CH3CH2OH + 1⁄2 O2 → CH3CHO + H2O

This method is one of the oldest routes for the industrial of preparation of acetaldehyde.

Acetaldehyde can also be produced by the hydration of acetylene, catalyzed by mercury salts. The reaction produces vinyl alcohol, which tautomerizes to acetaldehyde. This industrial route was dominant prior to the Wacker process.[20] One drawback of this process is the formation of polymerization and condensation products of acetaldehyde. Furthermore, it is costly and environmentally problematic, because the catalyst is methylated to give methylmercury during the process.

The wet oxidation process was used before the Wacker process was commercially established. With that method, Iron(III) sulfate is added to reoxidize the mercury metal to the mercury(II) salt to maintain required concentration of catalyst and avoid direct handling of mercury. Acetylene reacts at 90–95°C and the acetaldehyde formed is separated from water and mercury and cooled to 25–30°C. Iron(II) sulfate is formed in the reaction and is oxidized in a separate reactor with 30% nitric acid at 95°C. Pure acetaldehyde is obtained by fractional distillation of the aqueous solution at about 200 kPa.

Other methods

Traditionally, acetaldehyde was produced by the partial dehydrogenation of ethanol:

CH3CH2OH → CH3CHO + H2

In this endothermic process, ethanol vapor is passed at 260–290°C over a copper-based catalyst. The process was once attractive because of the value of the hydrogen coproduct,[19] but in modern times is not economically viable.

The hydroformylation of methanol with catalysts like cobalt, nickel, or iron salts also produces acetaldehyde, although this process is of no industrial importance. Similarly noncompetitive, acetaldehyde arises from synthesis gas with modest selectivity.[19]

Photo-induced keto-enol tautomerization is viable under atmospheric or stratospheric conditions. This photo-tautomerization is relevant to the earth's atmosphere, because vinyl alcohol is thought to be a precursor to carboxylic acids in the atmosphere.[23][24]

It is also a building block in the synthesis of heterocyclic compounds. In one example, it converts, upon treatment with ammonia, to 5-ethyl-2-methylpyridine ("aldehyde-collidine”).[31]

Acetal derivatives

Three molecules of acetaldehyde condense to form “paraldehyde,” a cyclic trimer containing C-O single bonds. Similarly condensation of four molecules of acetaldehyde give the cyclic molecule called metaldehyde. Paraldehyde can be produced in good yields, using sulfuric acid catalyst. Metaldehyde is only obtained in a few percent yield, often using HBr as a catalyst. At -40°C in the presence of acid catalysts, polyacetaldehyde is produced.[19]

Acetaldehyde forms a stable acetal upon reaction with ethanol under conditions that favor dehydration. The product, CH3CH(OCH2CH3)2, is in fact called "acetal".[32] although acetal is used more widely to describe other compounds with the formula RCH(OR')2

The global market for acetaldehyde is declining. Demand has been impacted by changes in the production of plasticizer alcohols, which has shifted because n-butyraldehyde is less often produced from acetaldehyde, instead being generated by hydroformylation of propylene. Likewise, acetic acid, once produced from acetaldehyde, is made predominantly by the lower-cost methanol carbonylation process.[35] The impact on demand has led to increase in prices and thus slowdown in the market.

China is the largest consumer of acetaldehyde in the world, accounting for almost half of global consumption in 2012. Major use has been the production of acetic acid. Other uses such as pyridines and pentaerythritol are expected to grow faster than acetic acid, but the volumes are not large enough to offset the decline in acetic acid. As a consequence, overall acetaldehyde consumption in China may grow slightly at 1.6% per year through 2018. Western Europe is the second-largest consumer of acetaldehyde worldwide, accounting for 20% of world consumption in 2012. As with China, the Western European acetaldehyde market is expected to increase only very slightly at 1% per year during 2012–2018. However, Japan could emerge as a potential consumer for acetaldehyde in next five years due to newfound use in commercial production of butadiene. The supply of butadiene has been volatile in Japan and the rest of Asia. This should provide the much needed boost to the flat market, as of 2013.[36]

Safety

Exposure limits

The threshold limit value is 25ppm (STEL/ceiling value) and the MAK (Maximum Workplace Concentration) is 50 ppm. At 50 ppm acetaldehyde, no irritation or local tissue damage in the nasalmucosa is observed. When taken up by the organism, acetaldehyde is metabolized rapidly in the liver to acetic acid. Only a small proportion is exhaled unchanged. After intravenous injection, the half-life in the blood is approximately 90 seconds.[19]

Dangers

Toxicity

Acetaldehyde is toxic when applied externally for prolonged periods, an irritant, and a probable carcinogen.[37] Acetaldehyde naturally breaks down in the human body[38] but has been shown to excrete in urine of rats.[39]

Irritation

Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat, and respiratory tract. This occurs at concentrations up to 1000 ppm. Symptoms of exposure to this compound include nausea, vomiting, and headache. These symptoms may not happen immediately. The perception threshold for acetaldehyde in air is in the range between 0.07 and 0.25 ppm.[19] At such concentrations, the fruityodor of acetaldehyde is apparent. Conjunctival irritations have been observed after a 15-minute exposure to concentrations of 25 and 50 ppm, but transient conjunctivitis and irritation of the respiratory tract have been reported after exposure to 200 ppm acetaldehyde for 15 minutes. It has a general narcotic action and large doses can even cause death by respiratory paralysis. It may also cause drowsiness, delirium, hallucinations, and loss of intelligence. Exposure may also cause severe damage to the mouth, throat, and stomach; accumulation of fluid in the lungs, chronic respiratory disease, kidney and liver damage, throat irritation, dizziness, reddening, and swelling of the skin.

Aggravating factors

Alzheimer's disease

People with a genetic deficiency for the enzyme responsible for the conversion of acetaldehyde into acetic acid may have a greater risk of Alzheimer's disease. "These results indicate that the ALDH2 deficiency is a risk factor for LOAD [late-onset Alzheimer's disease] …"[45]

Disulfiram

The drug disulfiram (Antabuse) prevents the oxidation of acetaldehyde to acetic acid. Antabuse is sometimes used as a deterrent for alcoholics wishing to stay sober.

Sources of exposure

Indoor air

Acetaldehyde is common contaminant in workplace, indoors, and ambient environments. Moreover, humans spend more than 90% of their time in indoor environments, increasing any exposure and the risk to human health.[47]

In a study in France, the mean indoor concentration of acetaldehydes measured in 16 homes was approximately seven times higher than the outside acetaldehyde concentration. The living room had a mean of 18.1±17.5 μg m−3 and the bedroom was 18.2±16.9 μg m−3, whereas the outdoor air had a mean concentration of 2.3±2.6 μg m−3.

It has been concluded that volatile organic compounds (VOC) such as benzene, formaldehyde, acetaldehyde, toluene, and xylenes have to be considered priority pollutants with respect to their health effects. It has been pointed that in renovated or completely new buildings, the VOCs concentration levels are often several orders of magnitude higher. The main sources of acetaldehydes in homes include building materials, laminate, linoleum, wooden varnished, and cork/pine flooring. It is also found in plastic water-based and matt emulsion paints, in wood ceilings, and wooden, particle-board, plywood, pine wood, and chipboard furniture.[48]

Outdoor air

The use of acetaldehyde is widespread in different industries, and it may be released into waste water or the air during production, use, transportation and storage. Sources of acetaldehyde include fuel combustion emissions from stationary internal combustion engines and power plants that burn fossil fuels, wood, or trash, oil and gas extraction, refineries, cement kilns, lumber and wood mills and paper mills. Acetaldehyde is also present in automobile and diesel exhaust.[49] As a result, acetaldehyde is "one of the most frequently found air toxics with cancer risk greater than one in a million."[12]

Cannabis smoke

Acetaldehyde has been found in cannabis smoke. This finding emerged through the use of new chemical techniques that demonstrated the acetaldehyde present was causing DNA damage in laboratory settings.[53]

Alcohol consumption

Many microbes produce acetaldehyde from ethanol, but they have a lower capacity to eliminate the acetaldehyde, which can lead to the accumulation of acetaldehyde in saliva, stomach acid, and intestinal contents. Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans.[54] According to European Commission's Scientific Committee on Consumer Safety's (SCCS) "Opinion on Acetaldehyde" (2012) the cosmetic products special risk limit is 5mg/l and acetaldehyde should not be used in mouth-washing products.[55]

Plastics

Acetaldehyde is also created by thermal degradation or ultravioletphoto-degradation of some thermoplastic polymers during or after manufacture. One common example occurs when a bottle of water is left in a hot car for a few hours on a hot, sunny day, and one notices its strange sweet taste in the water from the breakdown of the polyethylene terephthalate (PETE) container.[56] The water industry generally recognizes 20–40 ppb as the taste/odor threshold for acetaldehyde. The level at which an average consumer could detect acetaldehyde is still considerably lower than any toxicity.[57]

Dabit, a pharmacist in Nantes, France, performed a series of experiments and concluded that acetaldehyde was formed when hydrogen in ethanol combined with oxygen in sulfuric acid to form water: Dabit (1800) "Extrait du mémoire du cit. Dabit sur l'éther" (Extract of the memoire by citizen Dabit on ether), Annales de Chimie, 34: 289–305.

Fourcroy and Vauquelin stated that sulfuric acid was not consumed in the production of acetaldehyde: Fourcroy and Vauquelin (1800), "Sur l'éther préparé à la manière du cit. Dabit" (On the ether prepared in the way of citizen Dabit), Annales de Chimie, 34: 318-332.

↑ Liebig, J. (1835) "Sur les produits de l'oxidation de l'alcool" (On the products of the oxidation of alcohol), Annales de Chimie et de Physique, 59: 289–327. From p. 290: "Je le décrirai dans ce mémoire sous le nom d'aldehyde ; ce nom est formé de alcool dehydrogenatus." (I will describe it in this memoir by the name of aldehyde ; this name is formed from alcohol dehydrogenatus.)